Cost-Effectiveness of Pharmacogenomics-Guided Prescribing to Prevent Gene-Drug-Related Deaths: A Decision-Analytic Model

Wouden, Cathelijne H. van der; Marck, Heiralde; Guchelaar, Henk‐Jan; Swen, Jesse J.; Hout, Wilbert B. van den

doi:10.3389/fphar.2022.918493

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…Overall, the benefits and cost-effectiveness of implementing DPYD genotyping prior to FP dosing have been shown in several prospective trials and meta-analyses ( Meulendijks et al, 2015 ; Henricks et al, 2018 ; Brooks et al, 2022 ; Glewis et al, 2022 ; van der Wouden et al, 2022 ). Regulatory agencies such as the Food and Drug Administration (FDA) and European Medicine Agency (EMA), have moved towards recognizing the importance of the application of DPYD genotyping in clinical practice.…”

Section: Fluoropyrimidine Pharmacogenomicsmentioning

confidence: 99%

“…Pre-existing diseases, such as cardiovascular diseases (CVD), hepatic impairment, and renal insufficiency, as well as CVD risk factors (hypertension, hyperlipidemia and smoking), have been studied as for their association with increased risk for 5-FU-induced cardiotoxicity (Brutcher et al, 2018;Sara et al, 2018). The perception of incorporating non-genetic factors into polygenic risk score models is currently being evaluated for disease risk assessment (van Dam et al, 2023). This approach holds promise to increase the discriminative power of the often low variance explained solely by the genetic factors for the predictive outcome(s).…”

Section: A Polygenic Algorithm For Fp Dosing: New Challenges In Oncologymentioning

confidence: 99%

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Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm?

2023

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Fluoropyrimidines are chemotherapeutic agents widely used for the treatment of various solid tumors. Commonly prescribed FPs include 5-fluorouracil (5-FU) and its oral prodrugs capecitabine (CAP) and tegafur. Bioconversion of 5-FU prodrugs to 5-FU and subsequent metabolic activation of 5-FU are required for the formation of fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine triphosphate, the active nucleotides through which 5-FU exerts its antimetabolite actions. A significant proportion of FP-treated patients develop severe or life-threatening, even fatal, toxicity. It is well known that FP-induced toxicity is governed by genetic factors, with dihydropyrimidine dehydrogenase (DPYD), the rate limiting enzyme in 5-FU catabolism, being currently the cornerstone of FP pharmacogenomics. DPYD-based dosing guidelines exist to guide FP chemotherapy suggesting significant dose reductions in DPYD defective patients. Accumulated evidence shows that additional variations in other genes implicated in FP pharmacokinetics and pharmacodynamics increase risk for FP toxicity, therefore taking into account more gene variations in FP dosing guidelines holds promise to improve FP pharmacotherapy. In this review we describe the current knowledge on pharmacogenomics of FP-related genes, beyond DPYD, focusing on FP toxicity risk and genetic effects on FP dose reductions. We propose that in the future, FP dosing guidelines may be expanded to include a broader ethnicity-based genetic panel as well as gene*gene and gender*gene interactions towards safer FP prescription.

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Section: Fluoropyrimidine Pharmacogenomicsmentioning

confidence: 99%

Section: A Polygenic Algorithm For Fp Dosing: New Challenges In Oncologymentioning

confidence: 99%

Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm?

2023

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“…In addition, an interesting study reviewed 44 economic evaluations that investigated the cost-effectiveness of pharmacogenetic strategy. The study concluded that pharmacogenetic strategy produced both improved health outcomes and cost savings (van der Wouden et al, 2022).…”

Section: Genetic Human Evaluation Might Improve Studies In Pharmacoec...mentioning

confidence: 99%

“…Main examples of Pharmacogenomics emerged from clinical observation in differences on drug responses to standardized drugs dose and from observation on plasmatic and urinary concentration of the drug or its metabolites (W. Zhao & Meng, 2022). In this context, pharmacogenomics can help selecting the most appropriate pharmacological agent for a given patient and help the development of cost-effective treatments (Ross et al, 2012;van der Wouden, Marck, Guchelaar, Swen, & van den Hout, 2022). In this review we will approach the therapeutic implications of genetic differences and the Pharmacogenomics potential to improve drug treatments and its application in pharmaceutical industry.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomics: an opportunity for safer and efficient pharmacotherapy

Montes

de²,

Fontes-Dantas³

2022

RSD

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Responses to drugs are influenced by multiple factors, including health status, environmental influences, and genetic characteristics. The bioavailability of a drug can vary widely among individuals with a similar weight under the same drug dosage, which might result in toxicity and adverse drug reactions (ADRs). Genetic polymorphisms are known causes of interindividual differences in disease risk and treatment response in humans. In fact, a relevant number of associations between human genetic variants and predisposition to adverse events were described for diverse kinds of drug interactions, involving hundreds of proteins like receptors, transporters, and metabolizing enzymes. In this way, Pharmacogenetics and Pharmacogenomics emerged aiming to determine the genetic component responsible for drug response. A particular attention is showed if a treatment benefits (or harms) a particular subgroup, considering the interaction between treatment and genetic background. In this scenario, researchers have focused on better understanding personalized medicine, which holds the potential to maximize drug efficiency and minimize toxic effects. This review aims to introduce some principles, perspectives, and clinical applications of pharmacogenetics, emphasizing important findings and clinical applications that may contribute to therapeutical improvement.

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“…National Institute of General Medical Sciences, 2023 ). The incorporation of PGx information into the clinical care of patients aims to maximize therapeutic efficacy while minimizing adverse events and toxicities, thereby, improving patient outcomes and decreasing healthcare costs ( Jarvis et al, 2022 ; Morris et al, 2022 ; van der Wouden et al, 2022 ). The benefits of PGx guided therapy have been shown in multiple clinical settings ( Mega et al, 2010 ; Cavallari et al, 2018 ; Greden et al, 2019 ; Pereira et al, 2020 ; Oslin et al, 2022 ; Swen et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Evolution of pharmacogenomic services and implementation of a multi-state pharmacogenomics clinic across a large rural healthcare system

Van Heukelom,

Morgan,

Massmann

et al. 2023

Front. Pharmacol.

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Introduction: Pharmacogenomics (PGx) aims to maximize drug benefits while minimizing risk of toxicity. Although PGx has proven beneficial in many settings, clinical uptake lags. Lack of clinician confidence and limited availability of PGx testing can deter patients from completing PGx testing. A few novel PGx clinic models have been described as a way to incorporate PGx testing into the standard of care.Background: A PGx clinic was implemented to fill an identified gap in provider availability, confidence, and utilization of PGx across our health system. Through a joint pharmacist and Advanced Practice Provider (APP) collaborative clinic, patients received counseling and PGx medication recommendations both before and after PGx testing. The clinic serves patients both in-person and virtually across four states in the upper Midwest.Results: The majority of patients seen in the PGx clinic during the early months were clinician referred (77%, n = 102) with the remainder being self-referred. Patients were, on average, taking two medications with Clinical Pharmacogenetics Implementation Consortium guidelines. Visits were split almost equally between in-person and virtual visits.Conclusion: Herein, we describe the successful implementation of an interdisciplinary PGx clinic to further enhance our PGx program. Throughout the implementation of the PGx clinic we have learned valuable lessons that may be of interest to other implementors. Clinicians were actively engaged in clinic referrals and early adoption of telemedicine was key to the clinic’s early successes.

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Cost-Effectiveness of Pharmacogenomics-Guided Prescribing to Prevent Gene-Drug-Related Deaths: A Decision-Analytic Model

Cited by 14 publications

References 49 publications

Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm?

Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm?

Pharmacogenomics: an opportunity for safer and efficient pharmacotherapy

Evolution of pharmacogenomic services and implementation of a multi-state pharmacogenomics clinic across a large rural healthcare system

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